The present invention relates to a medicament for prevention and/or treatment of diabetes or diabetes complications, more specifically a medicament for prevention and/or treatment of diabetes or diabetes complications which comprises, as an active ingredient, a mixture of poly lactic acids having certain condensation degree.
Diabetes is a metabolic disorder mainly of glucose metabolism which is based on deficient secretion of insulin or reduced sensitivity of target cells thereof, and a major characteristic of diabetes is hyperglycemia. If hyperglycemia persists for a long period, serious complications such as retinopathy, nephropathy and neuropathy arise in various organs and nerves with angiopathy as a prime factor. Therefore, it is extremely important in the treatment of diabetes to control the blood sugar level and maintain it at a normal level, and the means for this purpose has been studied for many years.
Diabetes is classified according to the types of disease into insulin dependent diabetes (IDDM; type I diabetes) and non-insulin dependent diabetes (NIDDM; type II diabetes). In the case of non-insulin dependent diabetes (type II diabetes), onset of the disease is slow and insulin treatment is not necessarily required for maintaining life, and the blood sugar level can be controlled by a combination of diet therapy, kinesitherapy and drug therapy. In drug therapy, an insulin secretion promoting agent which is one type of oral agents for reducing the blood sugar level is widely and clinically used. However, since currently available insulin secretion promoting agents promote insulin secretion independent of blood sugar level, there arise problems that onset of serious hypoglycemia arises or the blood sugar level cannot be sufficiently controlled if the dosage is inadequate, and thus such agents are not satisfactory.
Therefore, if there is provided a novel medicament which can adequately control the blood sugar level and has little side effect, it is expected to be extremely useful for controlling the blood sugar level in diabetes patients.
An object of the present invention is to provide a medicament for prevention and/or treatment of diabetes or diabetes complications, which has an action of reducing the blood sugar level.
As a result of concentrated research to achieve the aforementioned object, the present inventors have found that the blood sugar level can be significantly reduced by administering a mixture of cyclic and/or straight chain poly lactic acids having a condensation degree of 3 to 19 to diabetes-induced model rats, thereby providing the present invention. Although it has been reported in the research up to now that a mixture of cyclic and/or straight chain poly L-lactic acids having a condensation degree of 3 to 19 is useful as an antineoplastic agent (Japanese Patent Application Laying-Open (Kokai) Nos. 9-227388 and 10-130153) and also as a QOL improving agent for cancer patients (Japanese Patent Application No. 11-39894 Specification; Bulletin of Japan Society of Clinical Oncology, Vol. 33, No.3, p. 493), the present inventors have found for the first time that it has an action of reducing the blood sugar level.
Thus, according to the first aspect of the present invention, there is provided a medicament for prevention and/or treatment of diabetes or diabetes complications which comprises, as an active ingredient, a mixture of cyclic and/or straight chain poly lactic acids having a condensation degree of 3 to 19.
According to another aspect of the present invention, there is provided a medicament for reducing the blood sugar level which comprises, as an active ingredient, a mixture of cyclic and/or straight chain poly lactic acids having a condensation degree of 3 to 19.
The medicament of the present invention may be used, in particular, for prevention and/or treatment of type II diabetes or complications thereof.
In a preferred embodiment of the present invention, the lactic acid which is a repeating unit in the poly lactic acid, substantially consists of L-lactic acid.
In one embodiment of the present invention, the mixture of cyclic and/or straight chain poly lactic-acids having a condensation degree of 3 to 19 that is used as an active ingredient, is a fraction obtained by condensing lactic acids (preferably lactic acid substantially consisting of L-lactic acid) by dehydration under an inactive atmosphere, subjecting the ethanol- or methanol-soluble fraction of the obtained reaction solution to reverse phase column chromatography, and eluting with 25 to 50 weight % acetonitrile aqueous solution of pH 2 to 3 and then with 90 weight % or more acetonitrile aqueous solution of pH 2 to 3.
Condensation of lactic acids by dehydration may be performed, for example, by stepwise decompression and temperature rise under a nitrogen gas atmosphere.
Moreover, reverse phase column chromatography may be performed applying ODS column chromatography.
According to another aspect of the present invention, there is provided the use of a mixture of cyclic and/or straight chain poly lactic acids having a condensation degree of 3 to 19 for the production of a medicament for prevention and/or treatment of diabetes or diabetes complications or a medicament for reducing the blood sugar level.
According to a further aspect of the present invention, there is provided a method for prevention and/or treatment of diabetes or diabetes complications or a method for reduction of the blood sugar level, which comprises a step of administering to mammals including humans, a therapeutically effective amount of a mixture of cyclic and/or straight chain poly lactic acids having a condensation degree of 3 to 19.